Genomic and epidemiological monitoring of yellow fever virus transmission potential.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

Phenotypic and functional characteristics of CD39high human regulatory B cells (Breg).

CD39 and CD73 are key enzymes in the adenosine (ADO) pathway. ADO modulates pathophysiological responses of immune cells, including B cells. It has recently emerged that a subpopulation of ADO-producing CD39+CD73+ B cells has regulatory properties. Here, we define the CD39high subset of these cells as the major contributor to the regulatory network operated by human B lymphocytes. Peripheral blood B cells were sorted into CD39neg, CD39inter and CD39high subsets. The phenotype, proliferation and IL-10 secretion by these B cells were studied by flow cytometry. 5'-AMP and ADO levels were measured by mass spectrometry. Agonists or antagonists of A1R, A2AR and A3R were used to study ADO-receptor signaling in B cells. Inhibition of effector T-cell (Teff) activation/proliferation by B cells was assessed in co-cultures. Cytokine production was measured by Luminex. Upon in vitro activation and culture of B cells, the subset of CD39high B cells increased in frequency (p < 0.001). CD39high B cells upregulated CD73 expression, proliferated (approximately 40% of CD39high B cells were Ki-67+ and secreted fold-2 higher IL-10 and ADO levels than CD39neg or CD39inter B cells. CD39high B cells co-cultured with autologous Teff suppressed T-cell activation/proliferation and secreted elevated levels of IL-6 and IL-10. The A1R and A2AR agonists promoted expansion and functions of CD39high B cells. CD39 ectonucleotidase is upregulated in a subset of in vitro-activated B cells which utilize ADO and IL-10 to suppress Teff functions. Proliferation and functions of these CD39high B cells are regulated by A1R- and A2AR-mediated autocrine signaling.

Preschool Denver Developmental Screening Test as a predictor of later school problems.

We compared three preschool tests as predictors of school problems at the end of first grade. A stratified sample of 113 4 1/2- to 5 1/2-year-old children, oversampling those at risk for developmental difficulties, was administered the Denver Developmental Screening Test (DDST), the Stanford-Binet IQ test (SB), and a two-stage shortened form of the DDST in the spring before school entry. Data from achievement tests, special class placement, and grade retention were obtained for 106 of the children at the end of first grade. Eighty-four percent of children with abnormal DDST scores had school difficulties by the end of first grade, compared with 47% of children with scores in the questionable range and only 15% of children in the normal range. Prediction from the SB was not as accurate; 72% of the children who scored less than 68 and 42% of those who scored between 68 and 84 on the preschool SB had school problems. Prediction for those children who had abnormal or questionable scores on the two-stage DDST was as good as prediction from the full DDST. However, far fewer of the total number of school problems were identified by the two-stage DDST. It appears that the DDST can be used on an individual basis for prediction of school problems.